The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1

Day 1

Dexamethasone

4 mg (PO)

60 minutes before chemotherapy

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Trastuzumab

8 mg/kg (IV infusion)

in 250 mL sodium chloride 0.9% over 90 minutes

(loading dose; cycle 1 only)

Day 8

Dexamethasone

4 mg (PO)

60 minutes before chemotherapy (can reduce or omit in cycle 2 if no nausea or vomiting)

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Cycle 2 and further cycles

Day 1

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Trastuzumab

6 mg/kg (IV infusion)

in 250 mL sodium chloride 0.9% over 30 minutes

(if the initial loading dose was well tolerated)

Day 8

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Frequency:

21 days

Cycles:

Continuous until disease progression or unacceptable toxicity. Trastuzumab monotherapy should be continued if vinorelbine is stopped for toxicity.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1

Day 1

Dexamethasone

4 mg (PO)

60 minutes before chemotherapy

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Trastuzumab

8 mg/kg (IV infusion)

in 250 mL sodium chloride 0.9% over 90 minutes

(loading dose; cycle 1 only)

Day 8

Dexamethasone

4 mg (PO)

60 minutes before chemotherapy (can reduce or omit in cycle 2 if no nausea or vomiting)

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Cycle 2 and further cycles

Day 1

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Trastuzumab

6 mg/kg (IV infusion)

in 250 mL sodium chloride 0.9% over 30 minutes

(if the initial loading dose was well tolerated)

Day 8

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

vinORELBine

30 mg/m2 (IV infusion)

in 50 mL sodium chloride 0.9% over 6 to 10 minutes. Consider commencing vinorelbine at 25 mg/m2 in patients who are heavily pre-treated or have poorer performance status.

Frequency:

21 days

Cycles:

Continuous until disease progression or unacceptable toxicity. Trastuzumab monotherapy should be continued if vinorelbine is stopped for toxicity.

Although hypersensitivity with trastuzumab is common, severe hypersensitivity reactions are uncommon. Use with caution in patients with dyspnoea at rest from pulmonary/cardiac conditions as increased risk of infusion related symptoms.

Premedication

Premedication only required if patient has had a previous hypersensitivity reaction and should be based on clinical judgement.

Emetogenicity LOW

Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.

Note: On days 1 and 8 of cycle 1, consider metoclopramide 10 mg and dexamethasone 4 mg prior to treatment. Can reduce or omit in cycle 2 if no nausea or vomiting.

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

In patients with a LVEF less than 45% and/or symptomatic heart failure HER-2 directed therapy should be avoided, except in the metastatic setting when breast cancer is life-threatening and where a cardiologist is also involved.

Concurrent anthracycline and HER-2 directed therapy is not recommended for extended periods of time.

Baseline and 3 monthly cardiac function tests are required during treatment. In the metastatic setting, after the first 12 months of therapy, if there are no cardiac complications, the frequency of cardiac assessments may be reduced at the discretion of the treating clinician unless there has been recent exposure to anthracyclines.

Assess prior to each treatment. Based on clinical findings, temporary omission, dose reduction or cessation of the vinca alkaloid may be indicated; review by medical officer before commencing treatment.

Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the antineoplastic regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information and reference committee consensus. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: all dose reductions are calculated as a percentage of the starting dose.

Haematological toxicity

ANC x 109/L (pre-treatment blood test)

1.0 to less than 1.5

Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well

0.5 to less than 1.0

Delay treatment until recovery

less than 0.5

Delay treatment until recovery and reduce vinorelbine by 25% for subsequent cycles

Febrile neutropenia or previous delay for myelosuppression

Delay treatment until recovery and reduce vinorelbine by 25% for subsequent cycles

Prolonged recovery greater than two weeks delay or 3rd delay for myelosuppression

Delay treatment until recovery and reduce vinorelbine by 50% for subsequent cycles or cease

Platelets x 109/L (pre-treatment blood test)

75 to less than 100

The general recommendation is to delay, however if the patient is clinically well it may be appropriate to continue treatment; refer to treating team and/or local institutional guidelines

50 to less than 75

Delay treatment until recovery

less than 50

Delay treatment until recovery and reduce vinorelbine by 25% for subsequent cycles

If treatment cannot be delivered on Day 8, then that treatment should be omitted rather than delayed. Treatment for the next cycle should proceed on the date originally scheduled and should incorporate dose modifications as appropriate.

No dose modification necessary
Give trastuzumab as soon as possible, i.e. do not wait until the next planned cycle

By more than 1 week

Reload trastuzumab with a dose of 8 mg/kg
Subsequent doses of 6 mg/kg should then be given every 3 weeks, according to the previous cycle
However, if the delay was due to cardiac toxicity, clinician may choose not to reload the patient

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.

Digoxin

Antineoplastic agents can damage the lining of the intestine; affecting the absorption of digoxin

Monitor digoxin serum levels; adjust digoxin dosage as appropriate

Antiepileptics

Both altered antiepileptic and antineoplastic levels may occur, possibly leading to loss of efficacy or toxicity

Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the antineoplastic therapy

Diminished response to vaccines and increased risk of infection with live vaccines

Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

Discharge information

Antiemetics

Laxatives

Patient information

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)

Extravasation, tissue or vein injury

The unintentional instillation or leakage of a drug or substance out of a blood vessel into surrounding tissue. This has the potential to cause damage to affected tissue.

Typically symmetrical sensory neuropathy, affecting the fingers and toes, sometimes progressing to the hands and feet. It is associated with several classes of antineoplastic agents. These include taxanes, platinum-based compounds, vinca alkaloids and some drugs used to treat multiple myeloma.

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, radiotherapy to the head, neck or oesophagus, and high dose chemotherapy followed by a blood and marrow transplant (BMT).

Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation.

Cardiotoxicity is a well recognised complication of HER-2 directed agents (e.g. trastuzumab, trastuzumab emtansine, pertuzumab). Mechanistically distinct from anthracycline-induced cardiotoxicity, it typically manifests as an asymptomatic decrease in the left ventricular ejection fraction (LVEF) and less commonly as congestive heart failure (CHF).

In preclinical studies of several HER-2 over-expressing breast cancer cell lines, vinorelbine has been demonstrated to act synergistically with trastuzumab.r

The evidence supporting this protocol comes from the HERNATA study by Andersson et al 2011. This was a phase III, randomised, multicentre trial comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab in patients with metastatic or locally advanced HER-2 positive breast cancer who were naïve to chemotherapy for advanced disease.r

Between May 2004 and August 2008, 143 patients were randomised to receive docetaxel 100 mg/m2 day 1 and 141 patients were assigned to vinorelbine 30-35 mg/m2 on days 1 and 8, both combined with trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance dose) on day 1 every 3 weeks.

The primary end point was time to progression (TTP) and secondary end points were overall survival (OS) and time to treatment failure (TTF). The study did not demonstrate superiority of either treatment arms in terms of efficacy. However, this study was not dimensioned to demonstrate non-inferiority.r

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Troubleshooting

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The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au